Shorter durations and lower doses of peginterferon alfa-2a are associated with inferior hepatitis B e antigen seroconversion rates in hepatitis B virus genotypes B or C

Y. F. Liaw, J. D. Jia, H. L.Y. Chan, K. H. Han, T. Tanwandee, W. L. Chuang, D. M. Tan, X. Y. Chen, E. Gane, T. Piratvisuth, L. Chen, Q. Xie, J. J.Y. Sung, C. Wat, C. Bernaards, Y. Cui, P. Marcellin

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Abstract

As there is currently a lack of consensus on the most appropriate dose and duration of peginterferon alfa-2a (PEG-IFNα-2a) therapy in hepatitis B e antigen (HBeAg)-positive patients, the efficacy and safety of either 24 or 48 weeks' duration and 90 μg/week or 180 μg/week doses were compared. HBeAg-positive patients (n = 544; 34% genotype B, 51% genotype C) were randomized to receive PEG-IFNα-2a (2 × 2 factorial design) for 24 or 48 weeks and at 90 μg/week or 180 μg/week and included in the per-protocol population. The primary efficacy endpoint of the noninferiority study was HBeAg seroconversion 6 months posttreatment. The prespecified odds ratio (OR) noninferiority margin was 1.88 with a one-sided significance level of 0.025. The highest rates of HBeAg seroconversion 6 months posttreatment were in the 180/48 arm (36.2% versus 14.1%-25.8% in the other arms). When the dose and duration arms were pooled, the OR for noninferiority of 24 weeks versus 48 weeks was 2.17 (95% confidence interval [CI] 1.43, 3.31; P = 0.749) and for 90 μg versus 180 μg was 1.79 (95% CI 1.18, 2.72; P = 0.410). As the upper limit of the 95% CI of the ORs were >1.88, 24 weeks were inferior to 48 weeks and 90 μg/week was inferior to 180 μg/week. The highest rates of response in the 180/48 arm were achieved by patients with HBsAg <1,500 IU/mL at Week 12 (58%) or Week 24 (57%), whereas patients with HBsAg >20,000 IU/mL did not respond. Adverse events were typical of those associated with PEG-IFNα-2a. Conclusion: Compared with lower doses and shorter durations, the licensed PEG-IFNα-2a treatment regimen (180μg/48 weeks) was the most efficacious and beneficial for HBeAg-positive patients predominantly infected with hepatitis B virus genotypes B or C.

Original languageEnglish
Pages (from-to)1591-1599
Number of pages9
JournalHepatology
Volume54
Issue number5
DOIs
Publication statusPublished - 2011 Nov

All Science Journal Classification (ASJC) codes

  • Hepatology

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    Liaw, Y. F., Jia, J. D., Chan, H. L. Y., Han, K. H., Tanwandee, T., Chuang, W. L., Tan, D. M., Chen, X. Y., Gane, E., Piratvisuth, T., Chen, L., Xie, Q., Sung, J. J. Y., Wat, C., Bernaards, C., Cui, Y., & Marcellin, P. (2011). Shorter durations and lower doses of peginterferon alfa-2a are associated with inferior hepatitis B e antigen seroconversion rates in hepatitis B virus genotypes B or C. Hepatology, 54(5), 1591-1599. https://doi.org/10.1002/hep.24555